Estrogen receptors in the human forebrain and the relation to neuropsychiatric disorders

The steroid hormone estrogen influences brain function and neuropsychiatric disorders, but neuroanatomical information about the estrogen receptors (E Rs) are rather limited. The main focus of this article is to provide an ove rview of the current status of the ER distribution and possible function in the human brain. The ERs are ligand activated transcription factors that b elong to the steroid hormone receptors, included in the nuclear receptor su perfamily. To date, there are two known ER subtypes, alpha and beta. In the human forebrain. both estrogen receptor subtypes are predominantly express ed in limbic-related areas, although they show distinct distribution patter ns. The ER alpha mRNA expression appears to dominate in the hypothalamus an d amygdala, indicating that the alpha -subtype might modulate neuronal cell populations involved in autonomic and reproductive neuroendocrine function s as well as emotional interpretation and processing. In contrast, the hipp ocampal formation, entorhinal cortex. and thalamus appear to be ER beta dom inant areas, suggesting a putative role for ER beta in cognition, non-emoti onal memory and motor functions. Clinical observations of estrogenic effect s together with the information available today regarding ER expression in the primate brain provide important clues as to the functional aspects of t he two ER subtypes. However, further characterization of the different phen otypes of the ER expressing cells in the human brain is needed as well as t he delineation of the genes which are regulated by the ERs and how this tra nscriptional control correlates with human behavior and mental status. (C) 2001 Elsevier Science Ltd. All rights reserved.